Sickle cell disease (SCD) is a common genetic disorder in African Americans, with a major impact on health and social well-being and a life expectancy of only 42 years. Individuals with SCD are known to be at increased risk of sudden cardiac death, the basis of which is not well understood. Investigating the genetic and environmental factors that contribute to sudden cardiac death in SCD should allow development of interventions aimed at reducing this health disparity in early mortality. We have recently reported a study showing that SCN5A-1103Y interacts with hypokalemia to promote LQT in a community-based population of African Americans, within the NHLBI Jackson Heart Study (JHS). However, whether SCN5A-1103Y or other genetic variants interact with the other QT-prolonging factors present in individuals with SCD, to contribute to LQT and the risk of sudden cardiac death, has not been studied before. At the University of Mississippi Medical Center, we have large pediatric and adult SCD clinics with over 1,200 patients, drawn from the same general community as participants in the JHS. We propose to study the interaction of SCN5A-1103Y and other genetic variants, with QT-prolonging factors present in SCD, on risk of LQT. This will provide a basis for future studies of the importance of the interaction of these genetic and secondary factors on clinical outcomes and management, with the long-term goal of decreasing the health disparity in mortality in individuals with SCD.